ABSTRACT/SUMMARY- Project 3 Age-related hearing loss (ARHL) ? presbycusis ? is a significant Public Health issue. It is the number one communication disorder and neurodegenerative condition of our aged population; and ranks as one of the top three chronic medical conditions, along with arthritis and cardiovascular diseases. Although much has been learned, the search is on for biomedical treatments that prevent, slow down or reverse the consequences of ARHL. In fact, there are no FDA-approved drugs to treat ARHL, despite a prevalence of over 40 million people in the US alone. The scope of Project 3 will delineate the functional effects on neural correlates of complex sound processing using different modulators of presbycusis. Specific Aim 1. Determine if hormonal supplementation can prevent or slow the progression of neural processing deficits observed in the aged auditory midbrain and cortex. Experimental approach: Neural correlates of temporally complex noise and signals-in-noise auditory stimulus paradigms will be assessed using multi-channel electrophysiology in animals undergoing aldosterone therapies. These measures will be compared with changes in biomarkers of aldosterone, and to behavioral correlates. Specific Aim 2. We will determine if exposing aging mice to an augmented acoustic environment (AAE) will improve neural correlates of sound processing deficits associated with presbycusis. Experimental approach: AAEs will consist of two extended, controlled exposures to specific temporally enriched and signal-in-noise background sounds presented in the free-field in the animal holding environment. Neural measures will characterize improvements in temporal processing and extraction of signals-in-noise, key features of ARHL at multiple levels of the auditory nervous system. Specific Aim 3. Determine the synergistic effects of aging and acquired hearing loss following drug- induced sensorineural hearing loss and unilateral conductive loss on auditory processing, and the neural bases of the therapeutic effect of transcranial magnetic stimulation to improve cortical maladaptive plasticity in the central auditory system. Experimental approach: Transcranial Magnetic Stimulation- TMS, has been shown to be effective in treating various disorders related to maladaptive cortical plasticity, but the neurophysiological mechanisms underlying the therapeutic benefits of TMS are unknown. We will measure neural correlates of central plasticity following acute hearing loss using multi-channel electrophysiology and cortical local-field potentials. A major focus of experiments will be the link between maladaptive plasticity and alteration in the interplay between neural excitation and inhibition.